Neonatal abstinence syndrome (NAS) is diagnosed in 55-94% or infants born to opioid-dependent mothers (American Academy of Pediatrics Committee on Drugs, 1998), and approximately 7000 at-risk infants are born in the United States each year (National Pregnancy and Health Survey, 1996). It is estimated that 2.8% of pregnant women use illicit drugs, and the problem is of course even larger when considered internationally. Hospitalization time for otherwise-healthy treated infants is prolonged, lasting from several weeks up to two months, which is a burden on both the parent and infant, and has a large financial impact. There is a need for improved treatment options. Simplistically, from the neonatal aspect of NAS, goals would include to safely decrease its incidence, severity, and duration, and thereby decrease the hospitalization time (and simultaneous separation from the parents) and exposure to other medications. Due to its partial mu opioid receptor agonist activity, high receptor affinity, and low intrinsic opioid activity, the pharmacological profile of buprenorphine greatly differs from that of methadone, the most widely used treatment for the mothers, and from that of morphine, one of the most widely used medical treatments for NAS. Experience with treatment of opioid-abusing, pregnant women with buprenorphine indicates that it is safe for the fetus, and that NAS in these infants may be less severe than is seen in infants exposed to methadone in utero. Treatment of NAS with buprenorphine, relative to morphine, should be safe and may result in shorter hospital stays for treated infants. This is an R21 application to establish treatment parameters for NAS with sublingual buprenorphine, and to establish its safety (IND #68403).